BOSTON, May 6, 2014 /PRNewswire/ -- Rhythm announced today the presentation of results from a Phase 2 clinical trial assessing the safety and efficacy of relamorelin (RM-131) in 204 patients with diabetic gastroparesis. Analysis of the data indicates that relamorelin administered twice daily for four weeks in patients with moderate to severe gastroparesis significantly improved gastric emptying, significantly reduced vomiting, and in a large (~60%) subgroup of the patients with vomiting at baseline, significantly improved a composite symptom score comprising nausea, abdominal pain, bloating, and early satiety. The study results were presented today in a late-breaker session at the Digestive Disease Week 2014 conference in Chicago.

"Patients with moderate to severe diabetic gastroparesis experience significant debility. Among the cardinal symptoms, vomiting can require the most significant medical intervention and is the leading cause for hospitalization in these patients," said Anthony Lembo, MD, Associate Professor of Medicine at Beth Israel Deaconess Medical Center and the lead author on the study. "There is a significant need for effective and well-tolerated new therapies for gastroparesis, and these Phase 2 results for relamorelin are very promising, particularly for the subgroup of patients with vomiting at baseline where there was also improvement in other symptoms including abdominal pain, bloating, and nausea."

Study ResultsThe Phase 2 clinical trial was designed to evaluate the effect of relamorelin on gastrointestinal (GI) motility, the symptoms of gastroparesis, and safety in patients with diabetic gastroparesis. The randomized, double-blind, placebo-controlled, adaptive, parallel-group study assessed relamorelin 10 mcg administered once daily, twice daily, or placebo-administered daily to patients with diabetic gastroparesis over a period of one month. The study's primary endpoint was gastric emptying.

In the oral presentation, "A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of RM-131 in Patients with Diabetic Gastroparesis," Dr. Lembo presented the following clinical data:

In a large subgroup of patients who had vomiting at baseline (~60% of patients), relamorelin significantly improved a composite endpoint including the other subjective symptoms of diabetic gastroparesisnausea, abdominal pain, bloating, and early satietyvs. placebo, in addition to improving gastric emptying and vomiting (post hoc analysis).

For the overall study group, there was a strong placebo effect for the subjective diabetic gastroparesis symptoms (nausea, abdominal pain, bloating, and early satiety), and relamorelin was associated with only numerical improvements vs. placebo that did not reach statistical significance.

Relamorelin was generally well tolerated, with little evidence of any safety concerns.

Study Design This study was a randomized, double-blind, placebo (pbo)-controlled, adaptive, parallel-group 28-day study, with a 1-week (wk) single-blind pbo run-in, where diabetic gastroparesis patients were randomized (1:1:1) to pbo, relamorelin 10 mcg s.c. QD (before the evening meal), and relamorelin 10 mcg s.c. BID (before breakfast and the evening meal). All patients received 2 injections per day. Patients (18-70y; BMI >18 kg/m2) with screening GE breath test (GEBT) T12 >79 min (1 SD above normal; with 75% of patients >2 SD above normal), Gastroparesis Cardinal Symptom Index greater than or equal to 2.6 and a history of nausea and/or vomiting greater than or equal to 1x/wk during the 2 weeks prior to screening were eligible. GEBT was performed at baseline and Day 28; a daily symptom diary recorded patient symptoms (nausea, abdominal pain, bloating, and early satiety) on a 0-10 scale. In addition, vomiting frequency and severity were recorded daily, and a composite of the four subjective symptoms was also analyzed. Scores were normalized to provide weekly symptom scores (Weeks 1, 2, 3, 4); the prespecified analysis was change from baseline (run-in week) to Week 4. Safety was evaluated including adverse events, ECG, laboratories, and weight.

"We are greatly encouraged with the results of this Phase 2 study of relamorelin, particularly the potential for treating vomiting, nausea, and abdominal pain, which are especially debilitating," said Keith Gottesdiener, MD, CEO of Rhythm. "We thank everyone who worked so hard to make this study a success, and we are now working to prepare for the next studies of relamorelin in diabetic gastroparesis and related GI functional disorders."

About Relamorelin (RM-131)Relamorelin is a small-peptide analog of ghrelin, a hormone produced in the stomach that stimulates gastrointestinal activity. Derived from the natural ghrelin sequence, relamorelin has been optimized to stimulate gastrointestinal (GI) motility, with greater potency and enhanced stability and pharmacokinetics. In Phase 1 clinical trials, RM-131 was effective in accelerating both gastric emptying and colonic transit and was shown to be safe and well-tolerated. Relamorelin has completed a Phase 2 study in diabetic gastroparesis, and additional Phase 2 trials are under way in lower GI functional disorders. The U.S. Food and Drug Administration (FDA) has granted Fast Track review status to relamorelin for the treatment of diabetic gastroparesis.

About GastroparesisGastroparesis affects a significant number of the 24 million diabetics in the U.S; an estimated 2.3 million type 1 and type 2 diabetic patients with moderate or severe gastroparesis symptoms are seeking treatment. Gastroparesis symptoms include nausea, vomiting, abdominal pain, and malnutrition and results in a significant rate of hospitalization. This condition also often undermines measures to manage hyperglycemia.

About Rhythm (WWW.RHYTHMTX.COM)Rhythm is a biotechnology company developing peptide therapeutics that address unmet needs in metabolic diseases. Rhythm is developing the ghrelin peptide agonist, relamorelin (RM-131), for the treatment of diabetic gastroparesis and other gastrointestinal functional disorders; and the MC4R peptide agonist, RM-493, for obesity and diabetes. Rhythm investors include MPM Capital, New Enterprise Associates, Third Rock Ventures, Ipsen, and Pfizer Ventures. The company is based in Boston, Massachusetts.